Endocrinology, Vol 129, 1909-1914, Copyright © 1991 by Endocrine Society

ARTICLES

Endothelins inhibit luteinization of cultured porcine granulosa cells

M Iwai, M Hasegawa, S Taii, N Sagawa, K Nakao, H Imura, S Nakanishi and T Mori
Department of Gynecology & Obstetrics, Faculty of Medicine, Kyoto University, Japan.

Endothelin (ET), a novel vasoconstrictor peptide containing three isopeptides [ET-1, ET-2, and ET-3 (ETs)], has various biological effects including vasoconstriction, mitogenesis, and steroidogenesis. We examined the ET-1-like immunoreactivity level in porcine follicular fluid and culture medium of porcine granulosa cells by RIA. The ET level in the follicular fluid was 9.4-14.2 pg/ml. These levels were within 0.42 to 0.62-fold of the porcine plasma level (22.7 +/- 3.1 pg/ml) (mean +/- SE). ET was detected in the culture medium of granulosa cells with and without LH treatment at the concentration of 56 +/- 9.3 and 4.9 +/- 1.2 pg/10(6) cells.h, respectively. We also examined whether ETs affect the luteinization of granulosa cells. ETs inhibited the LH-stimulated progesterone and cAMP accumulation in cultured porcine granulosa cells in a dose-dependent manner with an EC50 of 5 x 10(-11) M. ET-1, ET-2, and ET-3 (5 x 10(-8)M inhibited progesterone accumulation by 62.3 +/- 1.8, 59.8 +/- 4.0, and 63.3 +/- 5.7% in 6-day cultures, respectively, and significant inhibition was observed within 24 h of culture. ET-1, ET-2, and ET-3 (5 x 10(-8) M) inhibited the LH-stimulated cAMP accumulation in granulosa cells by 54.8 +/- 2.3, 55.4 +/- 7.1, and 55.5 +/- 6.2%, respectively, whereas they did not affect basal cAMP levels. As well as progesterone accumulation, ETs partially inhibited LH-stimulated morphological transformation of granulosa cells. In this study, we demonstrated that ET exists in follicular fluid and in the culture medium of granulosa cells, and that ET inhibited LH-induced progesterone accumulation, morphological transformation, and cAMP accumulation in cultured porcine granulosa cells. These findings suggest that ET acts as a modulator of steroid metabolism in preovulatory follicles.

This article has been cited by other articles:

				M. R. Hussein Apoptosis in the ovary: molecular mechanisms Hum. Reprod. Update, March 1, 2005; 11(2): 162 - 178. [Abstract] [Full Text] [PDF]

				F. Miceli, F. Minici, M. G. Pardo, P. Navarra, C. Proto, S. Mancuso, A. Lanzone, and R. Apa Endothelins Enhance Prostaglandin (PGE2 and PGF2{{alpha}}) Biosynthesis and Release by Human Luteal Cells: Evidence of a New Paracrine/Autocrine Regulation of Luteal Function J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 811 - 817. [Abstract] [Full Text]

				J. A. Flores Gene Expression of Endothelin-1 in the Porcine Ovary: Follicular Development Biol Reprod, November 1, 2000; 63(5): 1377 - 1382. [Abstract] [Full Text]

				B. D. Murphy Models of Luteinization Biol Reprod, July 1, 2000; 63(1): 2 - 11. [Abstract] [Full Text]

				A. Plonowski, A. K.Kaplinski, M. Radzikowska, M. Borowiec, and B. Baranowska Correlation between 21 amino acid endothelin, intrafollicular steroids and follicle size in stimulated cycles Hum. Reprod., September 1, 1999; 14(9): 2323 - 2327. [Abstract] [Full Text] [PDF]

				G. G. Nussdorfer, G. P. Rossi, L. K. Malendowicz, and G. Mazzocchi Autocrine-Paracrine Endothelin System in the Physiology and Pathology of Steroid-Secreting Tissues Pharmacol. Rev., September 1, 1999; 51(3): 403 - 438. [Abstract] [Full Text] [PDF]

				R. Zidovetzki, J.-L. Wang, J. A. Kim, P. Chen, M. Fisher, and F. M. Hofman Endothelin-1 Enhances Plasminogen Activator Inhibitor-1 Production by Human Brain Endothelial Cells via Protein Kinase C-Dependent Pathway Arterioscler. Thromb. Vasc. Biol., July 1, 1999; 19(7): 1768 - 1775. [Abstract] [Full Text] [PDF]

				J. A. McCracken, E. E. Custer, and J. C. Lamsa Luteolysis: A Neuroendocrine-Mediated Event Physiol Rev, April 1, 1999; 79(2): 263 - 323. [Abstract] [Full Text] [PDF]

				S. Yoshioka, H. Fujiwara, S. Yamada, K. Tatsumi, T. Nakayama, T. Higuchi, T. Inoue, M. Maeda, and S. Fujii Endothelin-Converting Enzyme-1 Is Expressed on Human Ovarian Follicles and Corpora Lutea of Menstrual Cycle and Early Pregnancy J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3943 - 3950. [Abstract] [Full Text]

				T. J. Acosta, A. Miyamoto, T. Ozawa, M. P.B. Wijayagunawardane, and K. Sato Local Release of Steroid Hormones, Prostaglandin E2, and Endothelin-1 from Bovine Mature Follicles In Vitro: Effects of Luteinizing Hormone, Endothelin-1, and Cytokines Biol Reprod, August 1, 1998; 59(2): 437 - 443. [Abstract] [Full Text]

				R. Mancina, T. Barni, A. E. Calogero, S. Filippi, S. Amerini, A. Peri, T. Susini, G. B. Vannelli, N. Burrello, G. Forti, et al. Identification, Characterization, and Biological Activity of Endothelin Receptors in Human Ovary J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 4122 - 4129. [Abstract] [Full Text] [PDF]

				G. C. Creatsas, A. B. Malamitsi-Puchner, E. A. Hassan, E. B. Economou, and D. I. Aravantinos Endothelin Plas{+/-}a Levels in Primary Amenorrheic Adolescents Before and After Estrogen Treatment Reproductive Sciences, November 1, 1996; 3(6): 350 - 353. [Abstract] [PDF]